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Biomedical subjects

H Mönig

Publications and source records attributed to H Mönig.

At least 73 records · Page 4Linked to original sources
PubMed1987

Bioavailability and elimination of nitrendipine in liver disease.

Twenty one patients with liver disease (cirrhosis 11, chronic hepatitis 5 and acute hepatitis 5) and 6 healthy volunteers were given a single i.v. dose of nitrendipine 5 mg. Afterwards nitrendipine 20 mg once daily were administered orally for seven days. With the intravenous injection a significant increase in the AUC and elimination half-life of nitrendipine was found in patients with cirrhosis as compared to the normal volunteers. After chronic oral dosing, the area under the plasma concentration-time curve, AUC (0-24), was 94.5 ng ml-1 h and the plasma clearance CL was 1380.6 ml/min in the healthy controls; in patients with cirrhosis the AUC (0-24) h was significantly greater at 309.4 ng ml-1 h and CL had fallen to 686.6 ml/min. Considerable accumulation of nitrendipine was also found in the patients with chronic hepatitis. Nitrendipine could not be detected in urine from any of the subjects. Blood pressure and heart rate were not significantly influenced by the treatment in the various groups investigated. Antipyrine clearance in the patients with cirrhosis was correlated with the nitrendipine plasma clearance. Thus, accumulation of nitrendipine has been demonstrated in the patients with cirrhosis and chronic hepatitis.

Administration, Oral↗
PubMed1987

On the effect of oxygen or copper(II) in radiation-induced degradation of DNA in the presence of thiols.

Degradation of DNA when gamma-irradiated in aqueous solutions containing cysteine can be efficiently enhanced not only with oxygen, but to the same extent also with Cu2+ ions under hypoxic conditions. The result can be explained by 'self-repair' in this system due to recombination of DNA. with RSS.-R intermediates, and repair inhibition by oxygen or copper involving RSS.-R scavenging. It is emphasized that oxygen enhancement in DNA-thiol systems may occur not only by peroxidation, via defect fixation (DNA-O2.) or thiol activation (RS-O2.), but also by the well-established inactivation of RSS.-R by oxygen. There is evidence also from literature data for a correlation between oxygen enhancement and RSS.-R stability, which varies with thiol concentration, pH and thiol structure.

Copper↗
PubMed1987

Pharmacokinetics of aldosterone in patients with Addison's disease: effect of rifampicin treatment on glucocorticoid and mineralocorticoid metabolism.

Treatment of tuberculosis with rifampicin in patients with pre-existing adrenal failure has been reported to induce adrenal crisis due to alteration of cortisol metabolism by induction of hepatic mixed liver oxygenase enzymes. To determine whether mineralocorticoid metabolism is altered by rifampicin treatment, we established the pharmacokinetics of immunoreactive aldosterone. The metabolic clearance rate (MCR) and plasma half-life of this material were measured before and after 6 days of rifampicin treatment (600 mg/day) in seven patients with Addison's disease due to tuberculosis. Antipyrine clearance and urinary 6-beta-hydroxycortisol excretion was determined to demonstrate induction of the cytochrome P450 dependent enzymes. Infusion of aldosterone at a constant rate of 0.17 mg/h over 4.5 h produced steady state concentrations after 2 h, with no difference before and after rifampicin treatment (mean +/- SD, 1649 +/- 144 vs 1586 +/- 80 pg/ml, respectively). The disappearance curve of IR-aldosterone from plasma was biexponential. No change could be observed in the plasma half-lives (alpha-phase 29 +/- 1.9 min vs 30 +/- 1.5 min, beta-phase 129 +/- 3.2 min vs 126 +/- 4.3 min), the MCR (1.47 +/- 0.1 l/h/kg vs 1.46 +/- 0.1 l/h/kg), and the volume of distribution (9.9 +/- 1.9 vs 10.2 +/- 0.3 l). The antipyrine half-life decreased significantly from 12.2 +/- 2.6 h to 7.6 +/- 0.9 h (P less than 0.05) with a rise in antipyrine clearance from 0.38 +/- 0.07 to 0.80 +/- 0.23 ml/min/kg (P less than 0.05) and no change in the volume of distribution.(ABSTRACT TRUNCATED AT 250 WORDS)

Addison Disease↗
PubMed1986

The influence of the solvent on the toxicity and radioprotective effect of thiophosphate WR2721 in mice.

The influence of various solvents on the toxicity as well as the protective efficiency of thiophosphate WR2721 in X-irradiated male mice is described. The use of Sörensen buffer as solvent with a pH-value of 7.4 leads to a statistically significant lower lethality in animals than aqua bidest. However, the radiation efficacy of thiophosphate with respect to the acute lethality within 30 days after irradiation is not influenced by the choice of the solvent used. A dose reduction factor of 2.49 +/- 0.03 is gained for the LD50/30 d at 500mg WR2721 per kg animal weight.

Amifostine↗
PubMed1986

[Effect of static magnetic fields on the prenatal development of the mouse].

Developmental effects were studied in pregnant albino-mice after exposures to a static homogeneous magnetic field (1 T) on days 7, 10 or 13 post conception (p.c.). These days correspond approximately to the 16th, 28th or 42nd day p.c. in human development and represent stages of increased sensitivity. Intrauterine effects (after exposures on days 7 or 10 p.c.) were evaluated. They included lethality, external malformations, disorders in the fetal skeleton and fetal weights. The evaluation of postnatal effects (after exposure on day 13 p.c.) included body-weight, brain weight, diameter of neocortex and commissures and the alignment of cortical neurons up to day 46 p.c. According to all these criteria, no development effects were observed after exposure to the magnetic field. Transient effects, that can be compensated or have no biological relevance cannot be excluded.

Animals↗
PubMed1985

Reactions of nitrogen dioxide in aqueous model systems: oxidation of tyrosine units in peptides and proteins.

By application of pulse radiolysis it was demonstrated that nitrogen dioxide (NO2.) oxidizes Gly-Tyr in aqueous solution with a strongly pH-dependent rate constant (k6 = 3.2 X 10(5) M-1 S-1 at pH 7.5 and k6 = 2.0 X 10(7) M-1 S-1 at pH 11.3), primarily generating phenoxyl radicals. The phenoxyl can react further with NO2. (k7 approximately 3 X 10(9) M-1 S-1) to form nitrotyrosine, which is the predominant final product in neutral solution and at low tyrosyl concentrations under gamma-radiolysis conditions. Tyrosine nitration is less efficient in acidic solution, due to the natural disproportionation of NO2., and in alkaline solutions and at high tyrosyl concentrations due to enhanced tyrosyl dimerization. Selective tyrosine nitration by interaction of NO2. with proteins (at pH 7 to 9) was demonstrated in the case of histone, lysozyme, ribonuclease A, and subtilisin Carlsberg. Nitrotyrosine developed slowly also under incubation of Gly-Tyr with nitrite at pH 4 to 5, where NO2. is formed by acid decomposition of HONO. It is recalled in this context that NO2.-induced oxidations, by regenerating NO2-, can propagate NO2./NO2- redox cycling under acidic conditions. Even faster than with tyrosine is the NO2.-induced oxidation of cysteine-thiolate (k9 = 2.4 X 10(8) M-1 S-1 at pH 9.2), involving the transient formation of cystinyl radical anions. The interaction of NO2. with Gly-Trp was comparably slow (k approximately 10(6) M-1 S-1), and no reaction was detectable by pulse radiolysis with Met-Gly and (Cys-Gly)2, or with DNA. Slow reactions of NO2. were observed with arachidonic acid (k approximately 10(6) M-1 S-1 at pH 9.0) and with linoleate (k approximately 2 X 10(5) M-1 S-1 at pH 9.4), indicating that NO2. is capable of initiating lipid peroxidation even in an aqueous environment. NO2.-Induced tyrosine nitration, using 50 microM Gly-Tyr at pH 8.2, was hardly inhibited, however, in the presence of 1 mM linoleate, and was not affected at all in the presence of 5 mM dimethylamine (a nitrosamine precursor). It is concluded that protein modifications, and particularly phenol and thiol oxidation, may be an important mechanism, as well as initiation of lipid peroxidation, of action of NO2. in biological systems.

Chemical Phenomena↗
PubMed1983

The early effect of sublethal X-irradiation of phagocytic cells in mouse blood and the influence of cystamine as measured by chemiluminescence.

The metabolic burst accompanying phagocytosis of granulocytes (PMN) leads to the generation of activated oxygen species such as O-2, H2O2, 1O2 and OH; which give rise to chemiluminescence (CL) in the presence of luminol. Reliable CL-measurements of stimulated PMN can be carried out in freshly drawn mouse blood, when photon counts are related to the number of PMN. Effects of low dose total body X-irradiation were studied using C57B1/6 mice. It was found that 24 and 48 hours after irradiation (0.24-0.95 Gy) CL of whole blood was slightly decreased. If however CL-counts were related to the number of PMN, an enhanced CL per single granulocyte was recorded. The administration of cystamine leads to an immune stimulating effect of unirradiated animals. In animals, who received 0.95 Gy a distinct radioprotective effect of cystamine can be observed.

Adenosine Diphosphate↗
PubMed1982

Haematological studies on 90Sr-90Y-toxicity: II. Femoral CFU-s kinetics and mitogen response of spleen cells.

Ferrokinetic perturbations in peripheral blood of mice treated with 90Sr-90Y were demonstrated previously. This paper deals with the effects of 90Sr-90Y treatment (2.5, 5, and 10 microCi/mouse), on the haemopoietic stem cell compartment and on the immune-status. The frequency and kinetics of haemopoietic stem cells in femoral marrow (determined as colony forming units in spleen, CFU-s) and their haemopoietic efficiency (as gauged by 59Fe- and 125IUdR-uptake) were estimated. The responsiveness of splenic lymphocytes of the same animals to mitogens (Con A, PHA, and LPS) were also measured. In all assays striking dose-dependent changes marked either by depressions or overshoots were observed during the first week post-incorporation. These are correlated with the pattern of deposition (primary and secondary) of the radionuclides 90Sr-90Y. Towards the end of the period of observation and presumably thereafter, the dependence on dose disappeared and the values remained subnormal. An exception to this was the response of splenic lymphocytes to mitogens. Much higher reactivity was recorded up to the end. This higher reactivity is attributed to augmented cellular turnover, the newly recruited lymphocytes (in accord with thier extreme radiosensitivity), being probably more reactive.

Animals↗
PubMed1981

Radioprotective and haemopoietic effects of some lipopolysaccharides from Rhodospirillaceae species in mice.

Lipopolysaccharides (LPS) from various Rhodopseudomonas and Rhodospirillum species were tested for their radioprotective efficiency against X-irradiation and for their influence on the growth of spleen colony forming units (CFU-s) in mice. The LPS from Rhodopseudomonas gelatinosa Dr2 gave a high survival rate. It also favoured CFU-s formation and erythroid differentiation.

Animals↗
PubMed1980

Haematological studies on 90Sr-90Y-toxicity. I. Ferrokinetic changes in peripheral blood of mice.

Erythropoietic changes were observed, measured by 59Fe-uptake into red blood cells, and on radioiron turnover from blood plasma, at different time intervals (2--64 days) after treating adult female mice with varying activities of 90Sr-90Y. Activities of 2.5 or 5.0 mu Ci radiostrontium per animal lead to a depression at time intervals of two and four days, at longer periods there was an overshoot. With activities of 0.5 or 1.0 mu Ci radiostrontium disturbances in the radioiron uptake are still observed, although these effects are not as pronounced as in experiments with higher burdens. In comparison with results obtained in experiments in which the plasma 59Fe-turnover was applied, even with an activity of 5 mu Ci radiostrontium per mouse, no deviation as against the untreated controls was detected.

Animals↗
PubMed1977

Characterization of microsomal electron transport components from control, phenobarbital- and 3-methylcholanthrene-treated mice. II. Improved resolution and quantitation of major components in ammonium sulfate fractions from total liver microsomes.

Quantitation of microsomal components in ammonium sulfate fractions using a high-resolution sodium dodecyl sulfate-polyacrylamide gel electrophoresis system, and a comparison of these results with those from similar experiments on total liver microsomes has enabled us to identify and better characterize the interactions between microsomal electron transport components. It was found that: (1) phenobarbital decreased the amount of one protein component of approximately 50 000 molecular weight while increasing a component of very similar molecular weight; (2) only two proteins appeared to be associated with CO binding; (3) another protein of approximately 68 000 molecular weight, one of the glycoproteins found in liver microsomes, appears to be induced by phenobarbital pretreatment; (4) the induction of NADPH-cytochrome c reductase activity after phenobarbital pretreatment is not dependent on an increase in the known NADPH-dependent flavoprotein, but rather on the increase in some component found predominately in our most soluble sub-microsomal fraction. A very good separation of the above components was achieved by ammonium sulfate fractionation, e.g. simply on the basis of their solubility. This and the fact that the more-or-less soluble proteins were induced by phenobarbital or 3-methylcholanthrene respectively indicate that the solubility of membrane proteins plays a major role in the structure and function of microsomal membranes.

Ammonium Sulfate↗
PubMed1977

Investigations on radical formation and inactivation of suspended trypsin after gamma-irradiation.

Crystalline trypsin was irradiated in oxygen-free suspension media of methanol, ethanol and n-heptane with 60Co-gamma-rays at 77 K or 273 K. Measurements with ESR and activity determinations revealed no influence of ethanol and n-heptane on the formation of free radicals and inactivation of trypsin. Especially, the results are independent on the polarity of the suspension media and correspond to an irradiation of trypsin in vacuum. On the other hand, methanol leads to a decay of radiation induced radicals and to an increased inactivation. The results are discussed in comparison to analogous experiments carried out with ultra-violet light.

Alkanes↗
PubMed1975

[Effect of aminopropyl-aminoethylthiphosphate on radio-iron utilization following whole-body irradiation of mice in the sublethal dose range].

The effectiveness of the thiophosphate compound WR 2721 was investigated with regard to the radiosensitivity of X-irradiated female mice in the sublethal dose range of 50 to 150 R using the radioiron test (59Fe). An increase of the radioresistance with regard to the radioiron uptake in young erythrocyte populations was obtained only beyond radiation doses of 75 R. In lower dose ranges the animals treated with thiophosphate became even more radiosensitive. At dose values of 100 R and 150 R dose reduction factors (DRF) of 1.3 and 1.5 respectively were obtained. These factors are considerably smaller than the DRF-values found for the survival rate at LD 50/30. A possible mechanism for this result may be due to the different dephosphorylation rate of the thiophosphate in various tissues, as described in literature.

Animals↗